{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:38:49Z","timestamp":1791113929338,"version":"4.1.0"},"reference-count":0,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1997,1,1]]},"abstract":"<jats:p> We have previously shown that serotonin (5-HT) induces both hyperplasia and hypertrophy of pulmonary artery smooth muscle cells (SMC) but not of endothelial cells (EC) through its high-affinity uptake. The present studies demonstrate rapid enhancement by 5-HT of Tyr phosphorylation of proteins, including p120, which also occurs in SMC but not in EC. The p120 protein was identified as GTPase-activating protein (GAP) by immunoprecipitation. Its phosphorylation occurred within minutes and preceded other events associated with 5-HT-induced mitogenesis. Tyr kinase (TK) and 5-HT uptake inhibitors and 8-bromoadenosine 3',5'-cyclic monophosphate blocked both the 5-HT-induced DNA synthesis and Tyr phosphorylation of GAP. Vanadate elevated DNA synthesis and Tyr phosphorylation of GAP of both control and 5-HT-treated cells. 5-HT failed to alter Tyr phosphorylation of GAP in cellular homogenates, as opposed to intact cells. In the presence of 3-isobutyl-1-methylxanthine, 5-HT inhibited cellular growth, presumably through its action on 5-HT1A or 5-HT4 receptors and elevation of adenosine 3',5'-cyclic monophosphate, but this was not associated with an alteration of Tyr phosphorylation of GAP. Similarly, a 5-HT1 or 5-HT2 receptor agonist failed to stimulate Tyr phosphorylation or DNA synthesis of SMC. Stimulation of cellular proliferation and enlargement produced by 1 microM 5-HT were totally abolished by TK inhibitors that did not affect 5-HT uptake. These data indicate that Tyr phosphorylation of GAP may act as an intermediate signal in 5-HT-induced mitogenesis of SMC which requires cellular internalization of 5-HT rather than its action on a membrane receptor. <\/jats:p>","DOI":"10.1152\/ajpcell.1997.272.1.c223","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T19:32:22Z","timestamp":1514143942000},"page":"C223-C230","source":"Crossref","is-referenced-by-count":35,"title":["Association of Tyr phosphorylation of GTPase-activating protein with mitogenic action of serotonin"],"prefix":"10.1152","volume":"272","author":[{"given":"S. L.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medicine, New England Medical Center\/Tufts UniversitySchool of Medicine, Boston, Massachusetts 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. W.","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, New England Medical Center\/Tufts UniversitySchool of Medicine, Boston, Massachusetts 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. L.","family":"Fanburg","sequence":"additional","affiliation":[{"name":"Department of Medicine, New England Medical Center\/Tufts UniversitySchool of Medicine, Boston, Massachusetts 02111, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","container-title":["American Journal of Physiology-Cell Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpcell.1997.272.1.C223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,17]],"date-time":"2024-06-17T19:32:44Z","timestamp":1718652764000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpcell.1997.272.1.C223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,1,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1997,1,1]]}},"alternative-id":["10.1152\/ajpcell.1997.272.1.C223"],"URL":"https:\/\/doi.org\/10.1152\/ajpcell.1997.272.1.c223","relation":{},"ISSN":["0363-6143","1522-1563"],"issn-type":[{"value":"0363-6143","type":"print"},{"value":"1522-1563","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,1,1]]}}}